The expression pattern of aquaporin-2 (AQP2), a vasopressin regulated member of the aquaporin gene family, in the cochlea and its potential role in Meniere's disease was investigated. RT-PCR screen of multiple rat tissues identified AQP2 transcripts in the cochlea, testis and kidney and an absence of tissue-specific splice variants. The level of AQP2 transcript in the cochlea was 10-fold lower relative to its expression in the testis and kidney. Western blot analysis demonstrated a single, 29 kDa band in the membrane fractions from cochlea, testis and the kidney. In the rat and mouse cochlea, AQP2 was expressed in the structures bordering the endolymph, including Reissner's membrane, the organ of Corti, inner and outer sulcus cells and the spiral limbus. A mutation screen of AQP2 in 12 individuals with Meniere's disease did not identify any sequence alterations or mutations within the four coding exons of AQP2 and their intron-exon junctions. The physiological role of AQP2 in water transport and its expression pattern in the cochlea suggests an important role for AQP2 in fluid homeostasis of the inner ear; however, its role in the pathogenesis in Meniere's disease remains to be established.